A team at Great Ormond Street Hospital made the discovery after examining the genomes of patients with debilitating movement disorders.
Photograph: Peter Macdiarmid/Getty Images

Doctors have discovered a new genetic disorder that robs children of the ability to walk normally and makes it hard for them to control their other limbs.

While the condition has never been defined before, researchers found that patients with the faulty DNA can benefit enormously from a medical treatment that uses electrical pulses to stimulate the brain.

What is a mutation?

Mutations are changes in the DNA code. They can be inherited from parents and turn up in almost every cell in the offspring, or they can be picked up during an organism's life and appear only in some tissues. Mutations can be acquired when DNA is not copied correctly during cell division, or when cells are exposed to environmental factors such as UV rays or chemicals in tobacco smoke. Mutations can range in size from tiny ones that alter only single units of the genetic code to much larger ones that change several genes at once.

In most cases, children who had the procedure regained better control of their arms and legs, and some improved so much they could walk again without help.

The team at Great Ormond Street Hospital in London made the discovery when they scoured the genomes of 27 patients with debilitating movement disorders which had left doctors baffled.

The analysis revealed that the patients had mutations in a single gene called KMT2B which is thought to play a central role in switching on other genes needed for the proper control of body movements. The corruption of the gene leads to what doctors call dystonia, when muscles contract involuntarily.

Patients who had faults in the KMT2B gene had similar problems to people with cerebral palsy, and some had even been diagnosed with the condition. The children typically had trouble walking, had an abnormal posture, and struggled to move their arms and hands as they wanted. As they grew up, their symptoms tended to get worse. “Even though it looks like cerebral palsy, it’s not cerebral palsy,” said Manju Kurian , a specialist in movement disorders who led the research.

Kurian found that in all but three cases, the genetic mutation had appeared spontaneously in her patients, an unlucky glitch in their early development. Of the three children who had inherited the mutation, only one of the six parents had any dystonia symptoms. “This is going to be a common cause of childhood dystonia,” she said. Details of the research are published in the journal Nature Genetics.

Doctors can already refer people with dystonia for what is called deep brain stimulation (DBS), but the treatment is a last resort, used only when drugs have failed. The procedure requires a major operation to insert two wires into the brain which run under the skin to a pulse generator implanted under the collarbone. It has long been used to alleviate movement problems in adults with Parkinson’s disease.

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When it is used to treat all forms of dystonia, DBS works well in some, but not in others. But Kurian noticed that the ten patients in her group who had been given DBS all improved. The younger ones seemed to fare best, to the point that some regained the ability to walk unaided. “So far all of the children we have seen seem to have a positive response,” she said.

One of the children in the study, 12-year-old Katie, is now due to have the DBS operation in January. Her mother, Sarah, said there was no sign of the disorder until Katie was aged two. “She seemed to trip over thin air,” Sarah said. “She was falling over so much.”

Katie was referred to a podiatrist who said the problem was down to her narrow gait. But by the age of five, Katie had not improved. It was several years later before Katie was referred to Great Ormond Street Hospital. There, it was clear to Kurian that Katie’s condition was getting worse. “It was hard for me to see the progression, but when you look back at photos it is really quite shocking,” Sarah said. “She used to run in sports day but can barely walk 10 steps now. She could ride a bike, but not any longer. She could hold a knife and fork, but now she can’t,” she said.

The diagnosis means an end to the uncertainty and the prospect of a treatment that has already helped other children. “The operation is obviously not something you want to put your child through,” Sarah said. “But when you look at where she started, and where she is now, you know you have to intervene.”